The readily available energy and pleasant taste of sugars make them potent contributors to the obesity epidemic. We have studied the neurobiology of reward-related feeding and propose to examine interactions between opioids, neuropeptides involved in sweet taste consumption, and oxytocin and melanocortins, which are associated with meal termination. The circuitry of these interactions includes the hypothalamic arcuate nucleus (ARC) and paraventricular (PVN) nuclei, and the central nucleus of the amygdala (CeA). Our hypothesis is that over-consumption of sweet foods/fluids occurs, in part, due to opioid-controlled inhibition of circuitry responsible for the termination of feeding, including oxytocin and alpha-MSH containing pathways. To test this hypothesis we propose: 1) To determine whether the hyperphagia associated with ingestion of sweet diets involves inhibition of oxytocin and alpha-MSH neurons in the PVN and ARC respectively; and 2) To determine whether PVN and CeA opioid receptors participate in sweet diet-induced hyperphagia by inhibiting termination of consumption (alpha-MSH to oxytocin) in response to acute versus chronic intake of rewarding diets rich in sugars. We will study the activation of neurons involved in the terminal portion of the meal (alpha-MSH to oxytocin) in response to acute versus chronic intake of diets rich in sugars. We speculate that orexigenic doses of an opioid receptor agonist will decrease activation of hypophagia- mediating alpha-MSH and oxytocin neurons. Similarly, acute exposure to a sweet palatable ingestant (which results in a modest level of intake compared to that observed during prolonged experience with an ingestant) leads to more robust activity within this pathway. These studies will help identify potential targets, both anatomical and neurochemical, which are involved in regulating ingestion of sweet fluids and/or diets and has important implications for obesity. [unreadable] [unreadable] [unreadable]